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Nutrients. 2019 Oct 19;11(10). pii: E2524. doi: 10.3390/nu11102524.

α-Lipoic Acid Inhibits IL-8 Expression by Activating Nrf2 Signaling in Helicobacter pylori-infected Gastric Epithelial Cells.

Author information

1
Department of Food and Nutrition, Brain Korea 21 PLUS Project, College of Human Ecology, Yonsei University, Seoul 03722, Korea. loveminb@naver.com.
2
Department of Food and Nutrition, Brain Korea 21 PLUS Project, College of Human Ecology, Yonsei University, Seoul 03722, Korea. jwlim11@yonsei.ac.kr.
3
Department of Food and Nutrition, Brain Korea 21 PLUS Project, College of Human Ecology, Yonsei University, Seoul 03722, Korea. kim626@yonsei.ac.kr.

Abstract

Helicobacter pylori (H. pylori) causes gastritis and gastric cancers. Oxidative stress is involved in the pathological mechanism of H. pylori-induced gastritis and gastric cancer induction. Therefore, reducing oxidative stress may be beneficial for preventing the development of H. pylori-associated gastric diseases. Nuclear factor erythroid-2-related factor 2 (Nrf2) is a crucial regulator for the expression of antioxidant enzyme heme oxygenase-1 (HO-1), which protects cells from oxidative injury. α-Lipoic acid (α-LA), a naturally occurring dithiol, shows antioxidant and anti-inflammatory effects in various cells. In the present study, we examined the mechanism by which α-LA activates the Nrf2/HO-1 pathway, suppresses the production of pro-inflammatory cytokine interleukine-8 (IL-8), and reduces reactive oxygen species (ROS) in H. pylori-infected AGS cells. α-LA increased the level of phosphorylated and nuclear-translocated Nrf2 by decreasing the amount of Nrf2 sequestered in the cytoplasm by complex formation with Kelch-like ECH1-associated protein 1 (KEAP 1). By using exogenous inhibitors targeting Nrf2 and HO-1, we showed that up-regulation of activated Nrf2 and of HO-1 results in the α-LA-induced suppression of interleukin 8 (IL-8) and ROS. Consumption of α-LA-rich foods may prevent the development of H. pylori-associated gastric diseases by decreasing ROS-mediated IL-8 expression in gastric epithelial cells.

KEYWORDS:

Helicobacter pylori; heme oxygenase-1; interleukine-8; nuclear factor erythroid-2-related factor 2; α-lipoic acid

PMID:
31635029
DOI:
10.3390/nu11102524
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